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Biography

Dr. Alexis is a cardiologist who takes care of patients with heart failure and patients who have received heart transplants and artificial hearts (VAD). Dr. Alexis' research focuses on left ventricular assist devices. His research is aimed at improving outcomes for patients with mechanical circulatory assist devices. He is board certified in Internal Medicine, Cardiovascular Disease and Advanced Heart Failure and Transplant Cardiology.

Professional Background

Dr. Alexis earned his M.D. from Harvard University in 1992. He was an intern and resident from 1992- 1995 at the Massachusetts General Hospital and completed his cardiology fellowship in 1998 at the Mount Sinai School of Medicine. He served on the faculty of the Mount Sinai School of Medicine (1998-2003) and joined the faculty of the University of Rochester in 2003 as an Assistant Professor of Medicine. He is Board Certified in Internal Medicine and Cardiovascular Disease. Dr. Alexis is a member of the heart failure/transplant section and his research focuses on left ventricular assist devices.

Research

Research in Dr. Alexis' lab focuses on signaling pathways that regulate intimal proliferation. Intimal proliferation occurs in several pathologic states including transplant arteriopathy and restenosis following angioplasty. Smooth muscle cell inflammation and proliferation are important aspects of this pathology. Our research focuses on the role of breakpoint cluster region (Bcr) in the development of intimal proliferation. Bcr was first identified for its role as part of the Philadelphia chromosome in chronic myelogenous leukemia. Bcr is also a serine/threonine kinase. We have demonstrated that Bcr plays a role in vascular wall intimal proliferation. We have shown that Bcr regulates both inflammation and proliferation in vascular smooth muscle cells (VSMC). Specifically, we have shown that dominant negative Bcr reversed Angiotensin II-mediated inhibition of the transcription factor PPAR gamma. We have found that Angiotensin II increases Bcr expression and kinase activation. We have shown that Bcr is present in the nucleus of smooth muscle cells and phosphorylates PPAR gamma. We have also shown that Bcr inhibits PPAR gamma transcriptional activation. This inhibition is via phosphorylation of PPAR gamma at S82, the site at which ERK 1/2 phosphorylates PPAR gamma (also leading to inhibition of PPAR gamma). Our data also demonstrate that Bcr enhances NF-kB transcriptional activity at least in part via inhibition of PPAR gamma. Intimal proliferation in low-flow carotid arteries was reduced in Bcr knockout mice compared with controls, demonstrating a critical role of Bcr on VSMC proliferation in vivo. Our current work focuses on Bcr signaling independent of PPAR gamma. We have identified the splicing factor UAP56 as another Bcr kinase substrate and we are now investigating the role of UAP56 in cellular proliferation.